Cladribine After Natalizumab for Multiple Sclerosis

Not currently recruiting at 1 trial location

Overseen By Rehana Hussain

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Texas Southwestern Medical Center

Must be taking: Natalizumab

Must not be taking: Corticosteroids, Cytokine treatments

Disqualifiers: PML, HIV, Hepatitis, TB, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for individuals with relapsing-remitting multiple sclerosis (RRMS) and active secondary progressive multiple sclerosis (active SPMS). Researchers aim to understand the safety and effectiveness of cladribine tablets after prior treatment with natalizumab. The trial seeks participants who have used natalizumab for at least a year without recent flare-ups. As a Phase 4 trial, this research provides insights into how the already FDA-approved treatment benefits more patients, offering valuable information for potential participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you have been on certain treatments like corticosteroids, cytokine treatments, or certain immunosuppressive therapies recently. It's best to discuss your specific medications with the trial team.

What is the safety track record for cladribine?

Research has shown that cladribine is generally well-tolerated by people with multiple sclerosis (MS). In one study, 270 patients who took cladribine experienced fewer relapses and new brain lesions, indicating the treatment works well without causing major side effects. Another report found that cladribine does not increase the risk of serious health problems, even with additional treatment courses. Importantly, no evidence suggests that cladribine increases the risk of problems during pregnancy. Overall, these findings suggest cladribine is a safe option for managing MS symptoms. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for multiple sclerosis, like interferons and glatiramer acetate, focus on modulating or suppressing the immune response to prevent flare-ups. Cladribine is unique because it targets specific immune cells, specifically lymphocytes, by reducing their numbers over time, helping to prevent the immune system from attacking the nervous system. Researchers are excited about cladribine because it is taken orally in a convenient tablet form, unlike some existing treatments that require injections or infusions. Additionally, cladribine's dosing schedule is less frequent, potentially improving patient adherence and quality of life.

What evidence suggests that cladribine might be an effective treatment for multiple sclerosis?

Research has shown that cladribine, which all participants in this trial will receive, effectively treats multiple sclerosis (MS). Studies have found that cladribine tablets significantly reduce relapses and decrease the size and number of new brain lesions in MS patients. In a 4-year study, nearly 9 out of 10 patients with relapsing MS did not experience disease progression. Additionally, cladribine lowered levels of a protein that signals nerve damage. Overall, these findings suggest that cladribine can be a strong option for managing MS symptoms and slowing the disease's progression. ^{1 6 7 8 9}

Who Is on the Research Team?

Olaf Stuve, MD, PhD

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 with relapsing forms of Multiple Sclerosis, including RRMS and active SPMS, who have been on natalizumab therapy for at least a year. Participants must weigh over 40 kg, not be pregnant or breastfeeding, use contraception effectively, and have no recent MS relapses. Exclusions include HIV or hepatitis infection, TB history, immunocompromised status, certain prior treatments like myelosuppressives or live vaccines recently.

Inclusion Criteria

I am not pregnant or breastfeeding.

I have been diagnosed with a relapsing form of MS.

Willing to provide voluntary and informed consent based on the Health Insurance Portability and Accountability Act (HIPPA)

Exclusion Criteria

I am positive for HIV or hepatitis B/C.

I have been diagnosed with or suspected to have PML.

I have been treated with cladribine before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Washout

A washout period of 14 to 28 days after the last infusion of natalizumab before starting cladribine treatment

2-4 weeks

Treatment Year 1

Participants receive cladribine 10 mg tablets in two cycles during the first year

12 months

Multiple visits for administration and monitoring

Treatment Year 2

Participants receive cladribine 10 mg tablets in two cycles during the second year

12 months

Multiple visits for administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

6-12 months

Open-label Extension

Participants may opt into a 2-year extension study with no intervention, monitoring clinical and paraclinical disease activity

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Cladribine

Trial Overview The study tests the safety and effects of cladribine tablets in patients previously treated with natalizumab. It aims to understand how cladribine impacts the disease's progression and immune response in those with Multiple Sclerosis after switching from another treatment.

How Is the Trial Designed?

Group I: Cladribine Experimental Treatment 1 Intervention

All study participants will receive treatment with cladribine 10 mg tablets at the recommended cumulative dose of 3.5 mg/kg, divided into 2 yearly treatment courses (1.75 mg/kg per treatment course). This regimen corresponds to the recommended dosage as per the USPI. Each treatment course is divided into 2 treatment cycles: * Administration of first treatment course (year 1 treatment): * First cycle: Starts on Day 1 of the study * Second cycle: Administered 23 to 27 days after the last dose of first cycle. * Administration of second treatment course (year 2 treatment): * First cycle: Administered at least 43 weeks after the last dose of year 1 treatment * Second cycle: Administered 23 to 27 days after the last dose of first cycle of year 2 treatment. The cycle dosage will be administered as 1 or 2 cladribine 10 mg tablets daily over 4 or 5 consecutive days.

Cladribine is already approved in United States, European Union for the following indications:

Approved in United States as Leustatin for:

• Hairy cell leukemia
• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin's lymphoma
• Multiple sclerosis

Approved in European Union as Litak for:

• Hairy cell leukemia
• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin's lymphoma

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

EMD Serono

Industry Sponsor

Trials

147

Recruited

27,800+

Dr. Shepard

EMD Serono

Chief Medical Officer since 2021

MD from University of Cincinnati Medical School, Fellowships in Hematology and Oncology at University of Chicago Hospitals and Clinics

Miguel Fernández Alcalde

EMD Serono

Chief Executive Officer

Bachelor's Degree in Pharmacy from the University Complutense in Madrid, MBA from the University of Alcalá de Henares, Master's Degree in Management from IESE Business School

Published Research Related to This Trial

In a 96-week phase III study involving 1,326 patients with relapsing-remitting multiple sclerosis, cladribine tablets demonstrated a safety profile with a high treatment completion rate (88.6% for cladribine vs. 86.3% for placebo).

The most common adverse event was lymphopenia, which aligns with cladribine's mechanism of action, and while infections were more frequent in the cladribine group (48.3% vs. 42.5% for placebo), they were mostly mild-to-moderate, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of cladribine tablets in multiple sclerosis: the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study. Cook, S., Vermersch, P., Comi, G., et al.[2022]

Cladribine is an effective oral treatment for very active recurring multiple sclerosis, requiring only two short courses of administration over two years to maintain efficacy for up to four years, significantly reducing flare-ups and disability progression compared to placebo.

While cladribine is generally safe, it can cause lymphopenia and increase the risk of herpes zoster infections; however, long-term follow-up (up to eight years) indicates no greater risk of serious events like cancers or opportunistic infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Recommendations for the use of cladribine tablets in recurring multiple sclerosis]. Oreja-Guevara, C., García-Merino, JA., Saiz, A., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12179467/

Cladribine tablets in the new multiple sclerosis era - PMC Several recent studies have demonstrated the efficacy of CladT in reducing serum NfL (sNfL) levels over a 2-year treatment period in RRMS ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2211034825004663

The real-world efficacy of Cladribine tablets and treatment ... In conclusion, the probability of first relapse was high in this nearly nationwide cohort of Finnish subjects treated with cladribine tablets for highly active ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33975489/

Effectiveness and safety of cladribine in MS: Real-world ... Results: Among 270 patients treated with cladribine, we observed a profound reduction of both relapses and new or enlarging MRI lesions.

4. emdserono.com emdserono.com/us-en/company/news/press-releases/new-mavenclad-4-year-data-highlighting-durable-effects.html

2025-09-17 New MAVENCLAD 4-year data highlighting ... Four-year data show nearly 9 in 10 RMS patients remained free from progression independent of relapse activity (PIRA); Results highlight the ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0022510X24002053

A real-world, single Centre study considering a two-year ... Our experience provides information for the 2-years after the last dose of CLAD, confirming a higher effectiveness of CLAD when placed early in the treatment ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10106322/

Safety and efficacy of cladribine in multiple sclerosis Our analysis showed that the PFS after cladribine use is 79% (95%CI 71%, 86%). Also, 58% of patients with MS who received cladribine remained ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2211034824006837

146. Post-Approval Safety of Cladribine Tablets in the ... While data are currently scant, there is no evidence for an increased risk of adverse pregnancy outcomes in patients receiving cladribine tablets. Recommended ...

8. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1626317/full

Cladribine tablets as therapy for advanced relapsing- ... Discussion: The results indicate that CladT is effective and safe in Polish patients with RRMS, characterized by high disease activity, delayed ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2211034825001403

First insights into the safety and effectiveness of additional ... Administering additional cladribine courses is an effective option to maintain disease control and did not trigger any serious adverse events attributable to ...